TCF1-LEF1 co-expression identifies a multipotent progenitor cell (TH2-MPP) across human allergic diseases.

Repetitive exposure to antigen in chronic infection and cancer drives T cell exhaustion, limiting adaptive immunity. In contrast, aberrant, sustained T cell responses can persist over decades in human allergic disease. To understand these divergent outcomes, we employed bioinformatic, immunophenotyping and functional approaches with human diseased tissues, identifying an abundant population of type 2 helper T (TH2) cells with co-expression of TCF7 and LEF1, and features of chronic activation. These cells, which we termed TH2-multipotent progenitors (TH2-MPP) could self-renew and differentiate into cytokine-producing effector cells, regulatory T (Treg) cells and follicular helper T (TFH) cells. Single-cell T-cell-receptor lineage tracing confirmed lineage relationships between TH2-MPP, TH2 effectors, Treg cells and TFH cells. TH2-MPP persisted despite in vivo IL-4 receptor blockade, while thymic stromal lymphopoietin (TSLP) drove selective expansion of progenitor cells and rendered them insensitive to glucocorticoid-induced apoptosis in vitro. Together, our data identify TH2-MPP as an aberrant T cell population with the potential to sustain type 2 inflammation and support the paradigm that chronic T cell responses can be coordinated over time by progenitor cells.

Predicting Postoperative Satisfaction with Breasts: How Important is the Preoperative BREAST-Q Score?

BACKGROUND: The role that preoperative Satisfaction with Breast plays in a patient's postoperative course after postmastectomy breast reconstruction (PMBR) is not understood. The aim of this study is to understand the impact of the preoperative score on postoperative outcome as an independent variable. METHODS: We examined patients who underwent PMBR between 2017 and 2021 and who completed the BREAST-Q Satisfaction with Breasts at 1 year postoperatively. Two multiple linear regression models (Model 1 with the preoperative Satisfaction with Breasts score and Model 2 without the preoperative score), likelihood ratio tests, simple t-statistics, and sample patient dataset to predict the 1 year score were performed. Multiple imputation was used to account for missing preoperative scores. RESULTS: Overall, 2324 patients were included. Model 1 showed that the preoperative score is significantly associated with the postoperative score (ß = 0.09, 95% confidence interval 0.04-0.14; p < 0.001). Comparing Model 1 and Model 2 demonstrated that including preoperative Satisfaction with Breasts in a regression significantly improves model fit (test statistic = 10.04; p = 0.0021). Using the absolute value of the t-statistics as a measure of variable importance in linear regression, the importance of the preoperative score was quantified as 3.39-more important than neoadjuvant radiation, mastectomy weight, body mass index, bilateral prophylactic mastectomy, and race, but less than adjuvant radiation, reconstruction type, and psychiatric diagnoses. CONCLUSION: Preoperative Satisfaction with Breasts scores are an important independent predictor of postoperative satisfaction after PMBR. Just as vital sign and work-up are carefully documented before surgery, preoperative scores should be collected to pre-emptively gauge patients' satisfaction and optimize postoperative outcomes.

Race and Ethnicity Impacts Patient-Reported Outcomes in Implant-Based Breast Reconstruction.

BACKGROUND: Addressing social determinants of health is critical in achieving health equity, and of the many determinants, race and ethnicity are key contributors in postmastectomy breast reconstruction. The purpose of this study was to investigate the impact of race and ethnicity on patient-reported outcomes (PROs) after implant-based breast reconstruction (IBBR) and to provide reference values for each cohort. METHODS: We identified all patients who underwent IBBR between January 2017 and August 2022 and completed the BREAST-Q longitudinally. Race and ethnicity were self-categorized as White, Asian, Black, or Hispanic. Reference values were established. Outcomes of interest were BREAST-Q scores preoperatively, and 6 months, 1 year, and 2 years postoperatively. Generalized estimating equation (GEE) modeling was performed to assess race and ethnicity as independent predictors of BREAST-Q scores. RESULTS: Overall, 3281 patients were included, of whom 2479 (75.6%) were White, 296 (9.0%) were Asian, 239 (7.3%) were Black, and 267 (8.1%) were Hispanic. There were significant differences in Physical Well-being of the Chest at all timepoints; Satisfaction with Breasts and Psychosocial Well-being at preoperative, 6 months, and 1 year; and in Sexual Well-being at 1 year. GEE modeling showed that relative to White patients, Asian subjects scored significantly lower on all BREAST-Q domains, while Black and Hispanic patients scored significantly lower on the Physical Well-being of the Chest domain. CONCLUSION: Racial and ethnic disparities persist within IBBR, with minority patients scoring lower on the BREAST-Q than White patients. This study suggests that more work is needed to understand and improve these PROs in minority patient populations. Individualized reference values may prove beneficial in assessing outcomes over time.

Breast-Conserving Therapy Versus Postmastectomy Breast Reconstruction: Propensity Score-Matched Analysis.

BACKGROUND: Although studies have compared patient-reported outcomes (PROs) after breast conserving-therapy (BCT) and postmastectomy breast reconstruction (PMBR), they often have been confounded by treatment or other factors that complicate a direct comparison. This study aimed to compare PROs after BCT and PMBR by using propensity score-matching analysis. METHODS: Patients who underwent BCT or PMBR between 2010 and 2022 and completed the BREAST-Q were identified. Each BCT patient was matched to a PMBR patient using nearest-neighbor 1:1 matching with replacement for each BREAST-Q time point. Outcomes included all prospectively collected BREAST-Q domains preoperatively, at 6 months, and at 1, 2, and 3 years postoperatively. A 4-point difference was considered clinically meaningful. RESULTS: For this study, 6215 patients (2501 BCT [40.2%] and 3714 PMBR [59.8%] patients) were eligible, and 2616 unique patients were matched. Preoperatively, 463 BCT and 463 PMBR patients were matched for analysis (6 months [443 matched pairs], 1 year [639 matched pairs], 2 years [421 matched pairs], 3 years [254 matched pairs]). At 6 months postoperatively, the BCT patients scored higher on all BREAST-Q domains than the PMBR patients (p < 0.05; differences > 4 points). At 1, 2, and 3 years, the patients who underwent BCT consistently had superior Satisfaction With Breasts, Psychosocial Well-Being, and Sexual Well-Being (p < 0.05), and the differences were clinically meaningful. CONCLUSION: In this statistically powered study, the BCT patients reported higher quality of life than the PMBR patients in early assessment and also through 3 years of follow-up evaluation. Given the equivalency in survival and recurrence outcomes between BCT and PMBR, patients eligible for either surgery should be counseled regarding the superiority of BCT in terms of PROs.

Frail but Resilient: Frailty in Autologous Breast Reconstruction is Associated with Worse Surgical Outcomes but Equivalent Long-Term Patient-Reported Outcomes.

BACKGROUND: Frailty is associated with higher risk of complications following breast reconstruction, but its impact on long-term surgical and patient-reported outcomes has not been investigated. We examined the association of the five-item modified frailty index (MFI) score with long-term surgical and patient-reported outcomes in autologous breast reconstruction. PATIENTS AND METHODS: We conducted a retrospective cohort study of consecutive patients who underwent mastectomy and autologous breast reconstruction between January 2016 and April 2022. Primary outcome was any flap-related complication. Secondary outcomes were patient-reported outcomes and predictors of complications in the frail cohort. RESULTS: We identified 1640 reconstructions (mean follow-up 24.2 ± 19.2 months). In patients with MFI ≥ 2, the odds of surgical [odds ratio (OR) 2.13, p = 0.023] and medical (OR 17.02, p < 0.001) complications were higher than in nonfrail patients. We found no significant difference in satisfaction with the breast (p = 0.287), psychosocial well-being (p = 0.119), or sexual well-being (p = 0.314) according to MFI score. Chronic obstructive pulmonary disease was an independent predictor of infection (OR 3.70, p = 0.002). Tobacco use (OR 7.13, p = 0.002) and contralateral prophylactic mastectomy (OR 2.36, p = 0.014) were independent predictors of wound dehiscence. Dependent functional status (OR 2.36, p = 0.007) and immediate reconstruction (compared with delayed reconstruction; OR 3.16, p = 0.026) were independent predictors of skin flap necrosis. Dependent functional status was also independently associated with higher odds of reoperation (OR 2.64, p = 0.011). CONCLUSION: Frailty is associated with higher risk of complications in breast reconstruction, but there is no significant difference in long-term patient-reported outcomes. MFI should be considered in breast reconstruction to improve outcomes in high-risk frail patients.

Reducing Disparities: Regional Anesthesia Blocks for Mastectomy with Reconstruction Within Standardized Regional Anesthesia Pathways.

BACKGROUND: Recent data suggest disparities in receipt of regional anesthesia prior to breast reconstruction. We aimed to understand factors associated with block receipt for mastectomy with immediate tissue expander (TE) reconstruction in a high-volume ambulatory surgery practice with standardized regional anesthesia pathways. PATIENTS AND METHODS: Patients who underwent mastectomy with immediate TE reconstruction from 2017 to 2022 were included. All patients were considered eligible for and were offered preoperative nerve blocks as part of routine anesthesia care. Interpreters were used for non-English speaking patients. Patients who declined a block were compared with those who opted for the procedure. RESULTS: Of 4213 patients who underwent mastectomy with immediate TE reconstruction, 91% accepted and 9% declined a nerve block. On univariate analyses, patients with the lowest rate of block refusal were white, non-Hispanic, English speakers, patients with commercial insurance, and patients undergoing bilateral reconstruction. The rate of block refusal went down from 12 in 2017 to 6% in 2022. Multivariable logistic regression demonstrated that older age (p = 0.011), Hispanic ethnicity (versus non-Hispanic; p = 0.049), Medicaid status (versus commercial insurance; p < 0.001), unilateral surgery (versus bilateral; p = 0.045), and reconstruction in earlier study years (versus 2022; 2017, p < 0.001; 2018, p < 0.001; 2019, p = 0.001; 2020, p = 0.006) were associated with block refusal. CONCLUSIONS: An established preoperative regional anesthesia program with blocks offered to all patients undergoing mastectomy with TE reconstruction can result in decreased racial disparities. However, continued differences in age, ethnicity, and insurance status justify future efforts to enhance preoperative educational efforts that address patient hesitancies in these subpopulations.

Remote Symptom Monitoring with Clinical Alerts Following Mastectomy: Do Early Symptoms Predict 30-Day Surgical Complications.

BACKGROUND: Electronic patient-reported outcome measures (ePROMs) for real-time remote symptom monitoring facilitate early recognition of postoperative complications. We sought to determine whether remote, electronic, patient-reported symptom-monitoring with Recovery Tracker predicts 30-day readmission or reoperation in outpatient mastectomy patients. METHODS: We conducted a retrospective review of breast cancer patients who underwent outpatient (< 24-h stay) mastectomy with or without reconstruction from April 2017 to January 2022 and who received the Recovery Tracker on Days 1-10 postoperatively. Of 5,130 patients, 3,888 met the inclusion criteria (2,880 mastectomy with immediate reconstruction and 1,008 mastectomy only). We focused on symptoms concerning for surgical complications and assessed if symptoms reaching prespecified alert levels-prompting a nursing call-predicted risk of 30-day readmission or reoperation. RESULTS: Daily Recovery Tracker response rates ranged from 45% to 70%. Overall, 1,461 of 3,888 patients (38%) triggered at least one alert. Most red (urgent) alerts were triggered by pain and fever; most yellow (less urgent) alerts were triggered by wound redness and pain severity. The 30-day readmission and reoperation rates were low at 3.8% and 2.4%, respectively. There was no statistically significant association between symptom alerts and 30-day reoperation or readmission, and a clinically relevant increase in risk can be excluded (odds ratio 1.08; 95% confidence interval 0.8-1.46; p = 0.6). CONCLUSIONS: Breast cancer patients undergoing mastectomy with or without reconstruction in the ambulatory setting have a low burden of concerning symptoms, even in the first few days after surgery. Patients can be reassured that symptoms that do present resolve quickly thereafter.

Impact of Mastectomy Flap Necrosis on Patient-Reported Quality-of-Life Measures After Nipple-Sparing Mastectomy: A Preliminary Analysis.

BACKGROUND: Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS: Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS: A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS: Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.

Early Complications in Prepectoral Tissue Expander-Based Breast Reconstruction.

BACKGROUND: Prepectoral implant placement for postmastectomy breast reconstruction has increased in recent years. Benefits of prepectoral reconstruction may include lack of animation deformities and reduced postoperative pain, but its complication profile is currently unclear. This study aimed to examine the complication profile of prepectoral tissue expanders (TEs) to determine factors associated with TE loss. METHODS: A retrospective review was performed to identify all patients who underwent immediate prepectoral TE reconstruction from January 2018 to June 2021. The decision to use the prepectoral technique was based on mastectomy skin quality and patient comorbidities. Patient demographics, comorbidities, and operative details were evaluated. Outcomes of interest included TE loss, seroma, hematoma, infection/cellulitis, mastectomy skin flap necrosis requiring revision, and TE exposure. Logistic regression analysis was performed to identify factors associated with TE loss. RESULTS: The study identified 1225 TEs. The most frequent complications were seroma (8.7%, n = 106), infection/cellulitis (8.2%, n = 101), and TE loss (4.2%, n = 51). Factors associated with TE loss in the univariate analysis included ethnicity, history of smoking, body mass index, mastectomy weight, and neoadjuvant chemotherapy. In the multivariate regression analysis, only mastectomy weight had a positive association with TE loss (odds ratio, 1.001; p = 0.016). CONCLUSION: Prepectoral two-stage breast reconstruction can be performed safely with an acceptable early complication profile. The study data suggest that increasing mastectomy weight is the most significant factor associated with TE loss. Further research examining the quality of the soft tissue envelope and assessing patient-reported outcomes would prove beneficial.

Breast cancer-related lymphedema: A comprehensive analysis of risk factors.

BACKGROUND: Breast cancer-related lymphedema is a devastating condition that negatively affects the quality of life of breast cancer survivors. We sought to identify risk factors that predicted the timing and development of lymphedema. METHODS: Women with breast cancer that underwent sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) at our institution between 2007 and 2022 were identified and sociodemographic and clinical information was extracted. We used logistic regression analysis to identify risk factors for lymphedema and performed cox-regression analysis to predict the timing of lymphedema presentation after surgery. RESULTS: We identified 1,223 patients, of which 161 (13.2%) developed lymphedema within 1.8 (mean, SD = 2.5) years postoperatively. Patients with SLNB had significantly lower odds for lymphedema development (vs. ALND, OR = 0.29 [0.14-0.57]). Patients between 40 and 49 years of age, and 50-59 (vs. <40 years, OR = 2.14 [1.00-4.60]; OR = 2.42, [1.13-5.16] respectively), African American patients (vs. Caucasian, OR = 1.86 [1.12-3.09]), patients with stage II, III, and IV disease (vs. stage 0, OR = 3.75 [1.36-10.33]; OR = 6.62 [2.14-20.51]; OR = 9.36 [2.94-29.81]), and patients with Medicaid (vs. private insurance, OR = 3.56 [1.73-7.28]) had higher rates of lymphedema. Cox-regression analysis showed that African American (HR = 1.71 [1.08-2.70]), higher BMI (HR = 1.03 [1.00-1.06]), higher stage (stage II, HR = 2.22 [1.05-7.09]; stage III, HR = 5.26 [1.86-14.88]; stage IV, HR = 6.13 [2.12-17.75]), and Medicaid patients (HR = 2.15 [1.12-3.80]) had higher hazards for lymphedema. Patients with SLNB had lower hazards for lymphedema (HR = 0.43 [0.87-2.11]). CONCLUSION: Lymphedema has identifiable risk factors that can reliably be used to predict the chances of lymphedema development and enable clinicians to educate patients better and formulate treatment plans accordingly. LEVEL OF EVIDENCE: III (Retrospective study).

The evolution of pediatric soft-tissue free flap reconstruction of the lower extremity after oncologic resection: A 30 year experience.

INTRODUCTION: Limb salvage has become the standard of care for lower extremity tumors because of improvements in adjuvant treatments and reconstructive techniques. While there is literature assessing pediatric lower extremity free flap reconstruction in the setting of trauma, there is a paucity of literature that analyzes oncologic free flap reconstruction in this patient population. We report our long-term experience and evolution of care for lower extremity oncologic free flap reconstruction in pediatric patients. METHODS: This is a retrospective case series of all patients ≤18 years of age who underwent oncologic soft-tissue microvascular reconstruction of the lower extremity, from 1992 to 2021. Data were collected for patient demographics, oncologic treatment, operative details, and post-operative outcomes. Functional outcomes were assessed by weight bearing status, ambulation, and participation in activities-of-daily-living (ADLs), and musculoskeletal tumor society (MSTS) scores. RESULTS: Over the 30-year study period, inclusion criteria were met by 19 patients (11 males, 8 females) with a mean age of 13.8 years and a mean follow-up of 5.3 years. At last follow-up, 13 patients (68.5%) were alive. The most common pathology was osteogenic sarcoma (13 patients, 68.5%). Sites of reconstruction were the hip (n = 1), thigh (n = 5), knee (n = 4), leg (n = 7), and the foot (n = 2). The most commonly used flaps were latissimus dorsi (n = 8), gracilis (n = 4), and anterolateral thigh ± vastus (n = 4). Postoperative complications occurred in nine patients (43%). Overall flap success rate was 95%. At latest follow-up, ambulation without assistive device was obtained in 11 patients (58%), full weight bearing was achieved by 13 patients (68.5%), and ADLs could be performed independently by 13 patients (68.5%). Mean MSTS score was 23.1/30. CONCLUSION: Microvascular reconstruction for oncological lower extremity defects in the pediatric population has high limb salvage rates and good functional outcomes.

Analysis of the microsurgery fellowship match: 2019-2022 update.

BACKGROUND: A recent analysis of microsurgery fellowship match data published in 2019 demonstrated increased competition for available positions. With growing opportunities in the field, the authors hypothesize that the landscape for both applicants and programs has become more competitive. The aim of this study is to compare two periods of match data to inform residents and programs in microsurgery. METHODS: Microsurgery fellowship match data was obtained from the San Francisco Match with approval by the American Society for Reconstructive Microsurgery for the years 2014-2022. Data were stratified into the categories of 2016-2018 and 2019-2022. Parameters assessed included: program and position fill rates, match rates, and in-service examination percentiles. Data were analyzed using Pearson's Chi-square tests and unpaired t-tests. RESULTS: The median number of participating programs and positions increased to 29 and 47 in 2019-2022, compared with 23 and 40 in 2016-2018. This coincided with a decrease in the number of applicants per position (1.3 [52-40] vs. 1.1 [50-47], p = .45). There was a significant increase in the match rate between groups (67.8% vs. 80.2%, p = .007). Recently, 2022 saw the lowest position fill rate on record, at 75.4% (40 of 53 positions filled), down from 85.3% (35 of 41) in 2018 (p = .35) and 95.6% (43 of 45) in 2019 (p = .006). Mean in-service examination percentiles for successfully matched applicants did not differ between (2016-2018) and (2019-2022) applicants. CONCLUSION: Recent years have seen a rise in the number of microsurgery fellowship training programs with a decline in the number of applicants. Accordingly, there has been an increased match rate for prospective applicants. Despite this, a pool of unmatched applicants and unfilled positions with training opportunities still remain. The reasons for which are likely multifactorial.

Comparisons of Impact of Vein Grafting with Different Indications on Outcomes of Reconstruction with Free Flaps.

BACKGROUND: Prior studies have shown an increased risk of complications and flap loss with the use of vein grafts in microsurgery. We hypothesize that indication for use of a vein graft can affect flap complications and loss rates. METHODS: We performed a retrospective review of all patients at our institution from 2010 to 2020 who underwent free flap reconstruction and required use of a vein graft. Indications for vein grafting included: salvage of flap during primary operation after microvascular compromise, augmentation of flow during primary operation, lengthening of the flap pedicle during the primary operation, and salvage of the flap during a secondary salvage operation after microvascular compromise. RESULTS: A total of 79 patients met the study inclusion criteria. There were significant differences among the vein graft indication groups and the following: area of reconstruction (p = 0.002), vein graft length (p = 0.018), vessels grafted (p = 0.001), vein graft donor site (p = 0.011), and total flap loss (p = 0.047). Of the four indications for vein grafting, salvage of the flap during secondary salvage operation after microvascular compromise had the highest rate of total flap loss (26.7%). There were no significant associations between other flap complications and vein graft indications. CONCLUSION: Vein graft use in the primary reconstructive setting is efficacious, with low risk of thrombosis. Use in secondary procedures, however, is associated with higher rates of total flap loss, likely due to the thrombotic process, which was initiated prior to the use of the graft resulting in the salvage procedure and not secondary to the graft itself.

Towards Patient-centered Decision-making in Breast Cancer Surgery: Machine Learning to Predict Individual Patient-reported Outcomes at 1-year Follow-up.

OBJECTIVE: We developed, tested, and validated machine learning algorithms to predict individual patient-reported outcomes at 1-year follow-up to facilitate individualized, patient-centered decision-making for women with breast cancer. SUMMARY OF BACKGROUND DATA: Satisfaction with breasts is a key outcome for women undergoing cancer-related mastectomy and reconstruction. Current decision-making relies on group-level evidence which may lead to suboptimal treatment recommendations for individuals. METHODS: We trained, tested, and validated 3 machine learning algorithms using data from 1921 women undergoing cancer-related mastectomy and reconstruction conducted at eleven study sites in North America from 2011 to 2016. Data from 1921 women undergoing cancer-related mastectomy and reconstruction were collected before surgery and at 1-year follow-up. Data from 10 of the 11 sites were randomly split into training and test samples (2:1 ratio) to develop and test 3 algorithms (logistic regression with elastic net penalty, extreme gradient boosting tree, and neural network) which were further validated using the additional site's data.AUC to predict clinically-significant changes in satisfaction with breasts at 1-year follow-up using the validated BREAST-Q were the outcome measures. RESULTS: The 3 algorithms performed equally well when predicting both improved or decreased satisfaction with breasts in both testing and validation datasets: For the testing dataset median accuracy = 0.81 (range 0.73-0.83), median AUC = 0.84 (range 0.78-0.85). For the validation dataset median accuracy = 0.83 (range 0.81-0.84), median AUC = 0.86 (range 0.83-0.89). CONCLUSION: Individual patient-reported outcomes can be accurately predicted using machine learning algorithms, which may facilitate individualized, patient-centered decision-making for women undergoing breast cancer treatment.

Efficacy of Immediate Lymphatic Reconstruction to Decrease Incidence of Breast Cancer-related Lymphedema: Preliminary Results of Randomized Controlled Trial.

OBJECTIVE: To conduct a randomized controlled trial (RCT) on the efficacy of immediate lymphatic reconstruction (ILR) for decreasing the incidence of breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND). BACKGROUND: Despite encouraging results in small studies, an appropriately powered RCT on ILR has not been performed. METHODS: Women undergoing ALND for breast cancer were randomized in the operating room 1:1 to either ILR, if technically feasible, or no ILR (control). The ILR group underwent lymphatic anastomosis to a regional vein using microsurgical techniques; control group had no repair and cut lymphatics were ligated. Relative volume change (RVC), bioimpedance, quality of life (QoL), and compression use were evaluated at baseline and every 6 months postoperatively up to 24 months. Indocyanine green (ICG) lymphography was performed at baseline and 12 and 24 months postoperatively. The primary outcome was the incidence of BCRL, defined as ≥10% RVC from baseline in the affected extremity at 12-, 18-, or 24-month follow-up. RESULTS: Of 72 patients randomized to ILR and 72 to control from January 2020 to March 2023, our preliminary analysis includes 99 patients with 12-month follow-up, 70 with 18-month follow-up, and 40 with 24-month follow-up. The cumulative incidence of BCRL was 9.5% in the ILR group and 32% in the control group ( P =0.014). The ILR group had lower bioimpedance values, decreased compression usage, better lymphatic function on ICG lymphography, and better QoL than the control group. CONCLUSIONS: Preliminary results of our RCT show that ILR after ALND decreases BCRL incidence. Our goal is to finish the accrual of 174 patients with 24-month follow-up.

The Impact of Psychiatric Diagnoses on Patient-reported Satisfaction and Quality of Life in Postmastectomy Breast Reconstruction.

OBJECTIVE: The purpose of this study was to determine the prevalence of psychiatric diagnoses among a sample of breast reconstruction patients and measure the association between these diagnoses and reconstruction-related, patient-reported outcomes. BACKGROUND: The impact of psychiatric disorders in conjunction with breast cancer diagnosis, treatment, and reconstruction have the potential to cause significant patient distress but remains not well understood. METHODS: A retrospective review of postmastectomy breast reconstruction patients from 2007 to 2018 at Memorial Sloan Kettering Cancer Center was conducted. Patient demographics, comorbidities, cancer characteristics, psychiatric diagnoses, and BREAST-Q Reconstruction Module scores (measuring satisfaction with breast, well-being of the chest, psychosocial, and sexual well-being) at postoperative years 1 to 3 were examined. Mixed-effects models and cross-sectional linear regressions were conducted to measure the effect of psychiatric diagnostic class type and number on scores. RESULTS: Of 7414 total patients, 50.1% had at least 1 psychiatric diagnosis. Patients with any psychiatric diagnoses before reconstruction had significantly lower BREAST-Q scores for all domains at all time points. Anxiety (50%) and depression (27.6%) disorders were the most prevalent and had the greatest impact on BREAST-Q scores. Patients with a greater number of psychiatric diagnostic classes had significantly worse patient-reported outcomes compared with patients with no psychiatric diagnosis. Psychosocial (ß: -7.29; 95% confidence interval: -8.67, -5.91), and sexual well-being (ß: -7.99; 95% confidence interval: -9.57, -6.40) were most sensitive to the impact of psychiatric diagnoses. CONCLUSIONS: Mental health status is associated with psychosocial and sexual well-being after breast reconstruction surgery as measured with the BREAST-Q. Future research will need to determine what interventions (eg, screening, early referral) can help improve outcomes for breast cancer patients with psychiatric disorders undergoing breast reconstruction.

Enhanced Surgical Decision-Making Tools in Breast Cancer: Predicting 2-Year Postoperative Physical, Sexual, and Psychosocial Well-Being following Mastectomy and Breast Reconstruction (INSPiRED 004).

BACKGROUND: We sought to predict clinically meaningful changes in physical, sexual, and psychosocial well-being for women undergoing cancer-related mastectomy and breast reconstruction 2 years after surgery using machine learning (ML) algorithms trained on clinical and patient-reported outcomes data. PATIENTS AND METHODS: We used data from women undergoing mastectomy and reconstruction at 11 study sites in North America to develop three distinct ML models. We used data of ten sites to predict clinically meaningful improvement or worsening by comparing pre-surgical scores with 2 year follow-up data measured by validated Breast-Q domains. We employed ten-fold cross-validation to train and test the algorithms, and then externally validated them using the 11th site's data. We considered area-under-the-receiver-operating-characteristics-curve (AUC) as the primary metric to evaluate performance. RESULTS: Overall, between 1454 and 1538 patients completed 2 year follow-up with data for physical, sexual, and psychosocial well-being. In the hold-out validation set, our ML algorithms were able to predict clinically significant changes in physical well-being (chest and upper body) (worsened: AUC range 0.69-0.70; improved: AUC range 0.81-0.82), sexual well-being (worsened: AUC range 0.76-0.77; improved: AUC range 0.74-0.76), and psychosocial well-being (worsened: AUC range 0.64-0.66; improved: AUC range 0.66-0.66). Baseline patient-reported outcome (PRO) variables showed the largest influence on model predictions. CONCLUSIONS: Machine learning can predict long-term individual PROs of patients undergoing postmastectomy breast reconstruction with acceptable accuracy. This may better help patients and clinicians make informed decisions regarding expected long-term effect of treatment, facilitate patient-centered care, and ultimately improve postoperative health-related quality of life.

Interpreting the BREAST-Q for Breast-Conserving Therapy: Minimal Important Differences and Clinical Reference Values.

BACKGROUND: The BREAST-Q is an important tool for evaluating patient satisfaction and quality of life in breast-conserving therapy (BCT) patients, but its clinical utility is limited by the lack of guidance on score interpretation. This study determines reference values and the minimal important difference (MID) for the BREAST-Q BCT module. METHODS: A retrospective review of BCT patients at Memorial Sloan Kettering Cancer Center from January 2011 to December 2021 was performed. Descriptive statistics were used to summarize median BREAST-Q scores. Distribution-based analyses estimated MIDs based on 0.2 standard deviation of baseline BREAST-Q scores and 0.2 standardized response mean of the difference between baseline and 1-year postoperative BREAST-Q scores. MIDs for different clinical groupings based on body mass index, radiation, and reexcision also were estimated. RESULTS: Overall, 8060 patients were included for determining reference values, and 5673 patients were included for estimating MIDs. Median BREAST-Q scores trended upwards and stabilized by 2 years after surgery for all domains except Physical Well-Being of the Chest, which decreased and stabilized by 2 years. A score interpretation tool, the Real-Time Engagement and Communication Tool, was created based on 25th percentile, median, and 75th percentile scores trajectories. All MID estimates ranged from 3 to 5 points; 4 points was determined to be appropriate for use in clinical practice and research. CONCLUSIONS: Reference values and MIDs are crucial to BREAST-Q score interpretation, which can lead to improved clinical evaluation and decision making and improved research methodology. Future research should validate this study's findings in different patient cohorts.

The Impact of Lymphedema on Patient-Reported Outcomes After Breast Reconstruction: A Preliminary Propensity Score-Matched Analysis.

BACKGROUND: Studies on the impact of secondary lymphedema on patient-reported satisfaction and quality of life following postmastectomy breast reconstruction are limited by their heterogeneity. We aimed to reduce heterogeneity in study sample populations and compare BREAST-Q Reconstruction Module scores of patients with lymphedema matched to patients without lymphedema. METHODS: We identified patients who underwent postmastectomy breast reconstruction from 2009 to 2017 and performed a propensity score-matched analysis to compare patient-reported outcomes of patients who developed lymphedema with those who did not. Matched covariates included age, body mass index, race/ethnicity, smoking history, radiation or chemotherapy exposure, postoperative infection, and reconstruction modality and laterality. Outcomes of interest were pre- and postoperative BREAST-Q scores for Satisfaction with Breasts, Physical Well-being of the Chest, Sexual Well-Being, and Psychosocial Well-Being; the minimal clinically important difference (MCID) was four points. RESULTS: Matched cohorts included 322 patients per group. Preoperative BREAST-Q scores did not differ between lymphedema and non-lymphedema matched cohorts. Postoperative BREAST-Q scores were significantly lower in lymphedema patients: Physical Well-Being of the Chest (all time points), Satisfaction with Breast (at 1 and 2 years), Sexual Well-Being (at 2 years), and Psychosocial Well-Being (at 2 and 3 years). All significant differences in average scores were greater than the MCID. CONCLUSIONS: Patients with breast cancer-related lymphedema reported significantly lower Physical Well-Being of the Chest, Satisfaction with Breasts, Sexual Well-Being, and Psychosocial Well-Being at various time points. Our findings may prove useful for patient counseling and justify the need for further research on the prevention and treatment of this devastating disease.

Strategies to avoid mastectomy skin-flap necrosis during nipple-sparing mastectomy.

BACKGROUND: Nipple-sparing mastectomy is associated with a higher risk of mastectomy skin-flap necrosis than conventional skin-sparing mastectomy. There are limited prospective data examining modifiable intraoperative factors that contribute to skin-flap necrosis after nipple-sparing mastectomy. METHODS: Data on consecutive patients undergoing nipple-sparing mastectomy between April 2018 and December 2020 were recorded prospectively. Relevant intraoperative variables were documented by both breast and plastic surgeons at the time of surgery. The presence and extent of nipple and/or skin-flap necrosis was documented at the first postoperative visit. Necrosis treatment and outcome was documented at 8-10 weeks after surgery. The association of clinical and intraoperative variables with nipple and skin-flap necrosis was analysed, and significant variables were included in a multivariable logistic regression analysis with backward selection. RESULTS: Some 299 patients underwent 515 nipple-sparing mastectomies (54.8 per cent (282 of 515) prophylactic, 45.2 per cent therapeutic). Overall, 23.3 per cent of breasts (120 of 515) developed nipple or skin-flap necrosis; 45.8 per cent of these (55 of 120) had nipple necrosis only. Among 120 breasts with necrosis, 22.5 per cent had superficial, 60.8 per cent had partial, and 16.7 per cent had full-thickness necrosis. On multivariable logistic regression analysis, significant modifiable intraoperative predictors of necrosis included sacrificing the second intercostal perforator (P = 0.006), greater tissue expander fill volume (P < 0.001), and non-lateral inframammary fold incision placement (P = 0.003). CONCLUSION: Modifiable intraoperative factors that may decrease the likelihood of necrosis after nipple-sparing mastectomy include incision placement in the lateral inframammary fold, preserving the second intercostal perforating vessel, and minimizing tissue expander fill volume.